スパルフロキサシン 化學(xué)特性,用途語(yǔ),生産方法
効能
抗菌薬, 核酸合成阻害薬
説明
Sparfloxacin is the most potent fluoroquinolone antibiotic introduced for the treatment
of community acquired infections. It has superior and broad in vitro activity against members
of family Enterobacferiaceae and anaerobic bacteria, some of which are resistant toβ-lactam
antibiotics or to aminoglycosides. In patients with surgical infections, sparfloxacin shows
excellent activity against resistant pathogens. It is effective in treating patients with bladder
irritability and is reported to have potential in the treatment of leprosy and Mycobacterium
tuberculosis in mice. Favorable pharmacokinetic properties, good intracellular penetration and
a lack of transferable resistance have been reported.
化學(xué)的特性
Light yellow powder
世界保健機(jī)関（WHO）
Sparfloxacin is a quinolone antimicrobial agent. See also under
quinolone and fluoroquinolone antimicrobial agents.
応用例（製薬）
It is highly active against most aerobic Grampositive cocci and Gram-negative bacilli, including fastidious Gram-negative bacilli, Acinetobacter spp., Campylobacter spp. and Legionella spp. Ps. aeruginosa is weakly susceptible. Activity also extends to the genital mycoplasmas, M. tuberculosis and M. avium complex isolates. It is moderately active against some anaerobes (including the B. fragilis group); L. monocytogenes is resistant.
It is well absorbed, achieving a plasma concentration of 1–1.5 mg/L 4.5 h after a 400 mg oral dose. Absorption is decreased in the presence of antacids owing to the formation of chelates with metallic ions. Concentrations in many tissues, including lung, exceed those in plasma. The plasma half-life is 15–20 h. CSF penetration is limited. Around 5–10% of a dose is eliminated unchanged in the urine, with about 30% appearing as the glucuronide. Total clearance is 10–15 L/h. The plasma half-life increases only modestly in renal failure to 30–40 h. About 50–60% of the dose appears as unchanged drug in the feces, mainly as the glucuronide, accounting for 10–20% of the administered dose.
Adverse events are those common to fluoroquinolones, in particular gastrointestinal tract disturbances, CNS effects (mainly headache and insomnia) and rashes. Photosensitivity reactions have been observed in 2–11% of patients. It can prolong the QTc interval and cases of torsade de pointes have been reported. It does not potentiate the toxicity of theophylline.
It has been used for respiratory and other infections caused by susceptible bacteria, but use has been restricted in the USA and Europe because of phototoxicity and cardiotoxicity.
臨床応用
Sparfloxacin, (cis)-5-amino-1-cyclopropyl-7-(3,5-dimethyl)-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, is a newer fluoroquinolone.
This compound exhibits higher potency against Grampositivebacteria, especially staphylococci and streptococci,than the fluoroquinolones currently marketed. It is also moreactive against chlamydia and the anaerobe Bacteroides fragilis.The activity of sparfloxacin against Gram-negative bacteriais also very impressive, and it compares favorably withciprofloxacin and ofloxacin in potency against Mycoplasmaspp., Legionella spp., Mycobacteria spp., and Listeria monocytogenes.Sparfloxacin has a long elimination half-life of18 hours, which permits once-a-day dosing for most indications.The drug is widely distributed into most fluidsand tissues. Effective concentrations of sparfloxacin areachieved for the treatment of skin and soft tissue infections,lower respiratory infections (including bronchitis and bacterialpneumonias), and pelvic inflammatory disease causedby gonorrhea and chlamydia. Sparfloxacin has also beenrecommended for the treatment of bacterial gastroenteritisand cholecystitis. The oral bioavailability of sparfloxacinis claimed to be good, and sufficient unchanged drug isexcreted to be effective for the treatment of urinary tract infections.Nearly 20% of an orally administered dose is excretedas an inactive glucuronide.
スパルフロキサシン 上流と下流の製品情報(bào)
原材料
Magnesium strip
Concentrated hydrochloric acid
シクロプロピルアミン
Iron mud
2,3,4,5-テトラフルオロ安息香酸
クロロエタン
テトラヒドロフラン
Ethanol solution
硝酸
塩化スルフィニル
炭酸ナトリウム
2,6-ジメチルピペラジン
3-Quinolinecarboxylic acid, 1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-, ethyl ester
3-Quinolinecarboxylic acid, 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-5-[(phenylmethyl)amino]-, ethyl ester
1-CYCLOPROPYL-5-AMIDO-6,7,8-TRIFLUORO-1,4-DIHYDRO-4-OXO-3- QUINOLINECARBOXYLIC ACID ETHYL ESTER
5-Amino-l-Cyclopropyl-6,7, 8-Trifluoro-1,4-Dihydro-4-Oxo-3-Quinolinearboxylic Acid
準(zhǔn)備製品